Formulation and method for relieving or preventing symptoms associated with uric acid crystals

ABSTRACT

A method for relieving or preventing symptoms associated with uric acid crystals, comprising consuming a formulation that supports three or more processes, the processes comprising:
         1) one that inhibits formation of uric acid in the body;   2) one that increases elimination of uric acid from the body; and   3) one that interferes with formation of uric acid crystals in the body.
 
A formulation, comprising: an extract of celery; an extract of cherry; and a lithium salt. Also, a process to make a formulation, comprising mixing together:
           i. a material that inhibits formation of uric acid in a body;   ii. a material that increases elimination of uric acid from the body;   iii. a material that interferes with formation of uric acid crystals in the body; and forming the mixture into a medicament.

FIELD OF THE INVENTION

This invention is directed to a method for relieving or preventingsymptoms associated with uric acid crystals, a formulation for relievingor preventing symptoms associated with uric acid crystals, a process tomake the formulation, and the formulation made by the process.

BACKGROUND OF THE INVENTION

Uric acid is an end product of nitrogen metabolism in the human body(the main product being urea), and is found in small amounts in bloodand urine. The disease ‘gout’ in humans is associated with abnormallyhigh levels of uric acid in the blood and in the urinary system and withthe formation of uric acid crystals in or near the joints. The symptomscaused by uric acid crystals include redness, swelling, inflammation,pain, kidney stones, and reduced movement. Increased concentration ofuric acid in the human blood stream may also result in one form ofkidney stones when the uric acid crystallizes into a solid inside thekidney. The uric acid crystals are made of salts of urate anions andcations including ammonium, sodium, potassium, calcium and magnesium.Ammonium urate is a uric acid crystal that often forms stones oruroliths in the urinary system. Sodium urate is a uric acid crystal thatoften causes symptoms in or near the joints in gout.

Medications such as NSAIDs, corticosteroids and allopurinol are commonlyused to treat gout. These medications are effective, but havesignificant adverse side-effects. None of these medications are known tobe mixed together into a single medicament.

Since the 1800s, colchicine has been a standard treatment for acutegout. Colchicine facilitates the elimination of uric acid from the body.While colchicine is effective, it often causes nausea, vomiting anddiarrhea. These side-effects are most common when this drug is takenorally, and because of their unpleasant nature, non-steroidalanti-inflammatory drugs (NSAIDs) have become the treatment of choice formost acute attacks of gout. The NSAID that is most widely used to treatacute gout is indomethacin. NSAIDs also have significant toxicity, butif used for the short-term, are generally well-tolerated.

Therapy directed at normalizing uric acid levels in the blood may beconsidered for patients who have had multiple gout attacks or who havedeveloped tophi or kidney stones. Several drugs that help the kidneyseliminate uric acid are available, such as probenecid, and a drug thatblocks production of uric acid by the body, such as allopurinol. Thechoice between these two types of drugs depends on the amount of uricacid in the urine.

What is desired are improved formulations for relieving symptomsassociated with uric acid crystals that are simple to administer,effective at reducing symptoms, have reduced toxicity, and are lessexpensive than formulations and treatments that are currently available.What are also needed are formulations for preventing symptoms associatedwith uric acid crystals in the body.

SUMMARY OF THE INVENTION

I have invented a method for relieving or preventing symptoms associatedwith uric acid crystals, comprising consuming a formulation thatsupports three or more processes that reduce a symptom due to uric acidcrystals in a body, the processes comprising:

1) a process that inhibits formation of uric acid in the body;

2) a process that increases elimination of uric acid from the body; and

3) a process that interferes with formation of uric acid crystals in thebody.

I have also invented a formulation for relieving or preventing symptomsassociated with uric acid crystals, comprising: an extract of celery; anextract of cherry; and a lithium salt.

I have also invented a process to make a formulation for relieving orpreventing symptoms associated with uric acid crystals, comprising:

a. mixing together:

-   -   i. a material that when consumed inhibits formation of uric acid        in a body;    -   ii. a material that when consumed increases elimination of uric        acid from the body;    -   iii. a material that when consumed interferes with formation of        uric acid crystals in the body; and

b. forming the mixture of step (a) into a medicament.

DETAILED DESCRIPTION

Additionally, I have invented a formulation for relieving or preventingsymptoms associated with uric acid crystals, comprising: three or morefood supplements that support three or more processes that reduce uricacid crystals in a body, wherein the formulation is made by a processcomprising:

a. making a mixture by combining the three or more food supplementstogether; and

b. forming the mixture into a medicament.

In one embodiment the method for relieving symptoms associated with uricacid crystals comprises consuming a formulation of an extract of celery,an extract of cherry, and a lithium salt.

An extract is a concentration of the active ingredients in a portion ofa leaf, stem, bark, flower, fruit, or seed. Extracts are made by anynumber of known methods, including steam extraction, alcohol extraction,solvent extraction, and supercritical fluid extraction.

The extract of celery may be from the leaves, stems, seeds, or root offresh or dried celery. One method to make celery seed extract isdescribed in U.S. Pat. No. 6,761,913. The method includes controlledethanolic extraction, distillation and drying, and further processing bysupercritical fluid extractions (SFE). The celery seed extract may befurther fractionated by column fractionation, distillation, LiAlHreduction and the like. The celery seed extract possesses activity forthe treatment and prevention of acute and chronic pain, inflammation andgastrointestinal irritation.

The extract of celery inhibits the formation of uric acid in the body.In one embodiment the extract of celery is standardized to contain atleast 50% 3-n-butylphthalide calculated as total phthalides. The extractof celery may be standardized to contain any level from at least 15% upto 85%, or even higher, or any amount in between, of 3-n-butylphthalide.

Commercial manufacturers of suitable celery seed extract includeNature's Herbs, Herbal Extracts Plus, Viable Herbal Solutions, andNatural Factors.

The extract of cherry may be from any portion of the fruit or plant,including the leaves, pit, bark, roots, etc. The cherry is from thegenus Prunus, and may be either sweet cherry (Prunus avium), tart cherry(Prunus cerasus), Amur choke cherry (Prunus maackii), Wild Black Cherry(Prunus serotina), or mixtures thereof. In one embodiment the cherryfruit extract is rich in flavonoids. These flavenoids are natural,potent antioxidants which support joint health. Flavonoids have alsobeen shown to support the health of collagen which makes up part of theskin, bones and connective tissue. Cherry fruit extract supports thebody's natural anti-inflammatory response, increases the elimination ofuric acid from the body, and contains powerful antioxidants to helpprevent damage to healthy cells. The extract may be prepared by knownextraction, distillation, and purification techniques well known in theart. In one embodiment the extraction is a supercritical fluidextraction. In one embodiment the cherry fruit extract is organic. Inone embodiment the extract of cherry is at least a 5:1, an 8:1, a 10:1concentrate or even higher.

Commercial manufacturers of cherry fruit extract include EnzymaticTherapy Inc., Herbal Extraction Group Inc., Neutraceutical SciencesInstitute, and NOW Foods.

Lithium salt is one ingredient that may be used in the formulation whichinterferes with formation of uric acid crystals in the body. Lithiumions in the blood and urine make the uric acid more soluble so that itdoesn't form crystals as readily. Lithium salt may be in any number ofdifferent forms, including, but not limited to lithium orotate, lithiumproteinate, lithium aspartate, lithium citrate, lithium carbonate, andmixtures thereof.

In one embodiment, the formulation that is used for relieving symptomsassociated with uric acid crystals comprises from 25 to 200 mg ofextract of celery, from 100 to 1500 mg extract of cherry, and from 1.5to 10 mg of lithium in the lithium salt in a medicament. The formulationin the medicament is consumed from one to four times a day. The numberof times per day can be increased depending on the severity of symptoms.

The medicament is a substrate for providing a single dose of theseparate components of, or a mixture of, the complete formulation. Themedicament, for example, may be a tablet, a capsule, a pill, a softgel,a suspension, a chewable, a lozenge, or a powder. Thus the formulationmay be given in separate medicaments, or in a combined mixture in asingle medicament. An advantage of a combined mixture in a singlemedicament is that a patient consuming the formulation needs to takefewer medicaments, and in some embodiments less inert filler is used inthe formulation. In some embodiments the wt % inert filler is less than10 wt %, less than 5 wt %, or even none at all. Examples of inertfillers are materials also known as excipients. Inert fillers may beused to help bind, preserve, or give bulk to the formulation. Inertfillers may also be used to color, flavor, or change the texture of theformulation.

Capsules are one medicament that can be used. Capsules come in a widevariety of sizes, and there are some that are vegetarian. Someadvantages of capsules are that they are generally easy to swallow,dissolve more readily than some other medicaments, and they requirelower amounts of (or no amount of) inert filler.

In one embodiment the formulation is a high dose formulation that iseffective for relieving the symptoms associated with uric acid crystalsduring an acute phase of gout. A high dose formulation contains from 100to 200 mg of extract of celery, from 250 to 1500 mg extract of cherry,and from 3 to 10 mg lithium in the lithium salt, in one or moremedicaments. In another embodiment the formulation is a low doseformulation that is effective for preventing the symptoms associatedwith recurring or chronic gout, kidney stones, or a combination thereof.A low dose formulation contains from 25 to 150 mg of extract of celery,from 100 to 1000 mg of extract of cherry, and from 1.5 to 7.5 mg oflithium in the lithium salt. In one embodiment, the formulation (in oneor more medicaments) is consumed one to four times per day.

The method for relieving symptoms associated with uric acid crystals iseffective for relieving and preventing the pain symptoms of gout, kidneystones, or combinations thereof.

In one embodiment all the constituents of the formulation are foodsupplements that are readily available, and have a very low toxicity. Insome embodiments the formulation is a mixture of at least three foodsupplements and is in the form of dry particles, such as a powder,flakes, or granules. In one aspect the formulation is made to a specificblend in a medicament, wherein the medicament is consumed in amounts andat a frequency that is effective for preventing symptoms associated withuric acid crystals, and wherein the medicament is consumed in higheramounts and/or at a higher frequency that is more effective forrelieving symptoms associated with uric acid crystals. For example, anindividual may take one capsule of the formulation every other day toprevent symptoms and may take one to three capsules of the formulationthree times a day to relieve symptoms. The highest dose is selected toassure safety and is adjusted to the specific formulation in themedicament.

One advantage in some embodiments of the invention is that the level oflithium in the formulation is low enough so that when it is consumed ineffective amounts it does not require blood monitoring. The level oflithium does not build up to toxic levels, unlike what can occur withearlier known lithium treatments for reducing uric acid crystals in thebody. The levels of the lithium salt in the formulation are much lowerthan what would have been expected to be effective for interfering withformation of uric acid crystals in the body by earlier known methods.This is possible due to the synergistic effect of using a material thatinhibits formation of uric acid in a body and a material that increaseselimination of uric acid from the body along with the lithium salt.

Another side-benefit of the method of this invention is improved mentalfunctioning caused by improvements in at least two physiochemicalprocesses in the brain. The celery seed extract prevents and improvesdementia. The use of n-butylphthalide for this purpose is taught in USPatent Publication 2007/0265336 A1. The lithium stabilizes mood. Tartcherries are also a rich source of melatonin. Besides helping regulatethe body's sleep cycle, melatonin is an antioxidant that's able to breakthrough the brain barrier and provide direct antioxidant protection tothe delicate structures within brain cells. Melatonin is believed tohave strong neuroprotective properties, promoting brain healththroughout the aging process.

EXAMPLES

The invention will be further explained by the following illustrativeexamples that are intended to be non-limiting.

Example 1

The following three dietary supplements were purchased at iHerb:

-   -   Natural Factors, Celery Seed Extract, 60 Capsules for $11.97.        Each capsule contained 75 mg celery (Apium graveolens) seed        extract (standardized to contain 85% 3-n-butylphthalide        calculated as total phthalides)    -   Enzymatic Therapy, Cherry Fruit Extract, 180 Capsules for        $20.27. Each capsule contained 500 mg of sweet cherry (Prunus        avium) fruit extract, in a 10:1 concentrate by weight.    -   Nutrient Carriers Incorporated, Advanced Research, Lithium        Orotate, 120 mg, 200 Tablets for $15.00 Each tablet contained        4.9 mg elemental lithium.

A 54 year old man weighing approximately 300 lbs, who was experiencingrecurring episodes of gout approximately every few months, was selectedfor treatment. This man was not known to be taking any other medicationsat the time of treatment. During one severe episode of gout, thefollowing treatment was provided, and was continued for several months:

-   -   1 capsule of celery seed extract—taken three times per day, 1        capsule of cherry fruit extract—taken three times per day, and 1        tablet of lithium orotate—taken twice a day.

The man noticed an improvement in gout symptoms in three to four weeks,and the symptoms let up completely within four to six weeks. Thetreatment has continued for five months, with no re-occurrence ofsymptoms and no adverse side-effects. The man attributes the improvementin gout symptoms to the treatment.

Example 2

A 51 year old man weighing approximately 155 lbs, who experienced goutsymptoms occasionally (approximately once or twice a year) was selectedfor treatment. This man was known to be taking multiple foodsupplements, including 3 gm of Vitamin C and multiple herbs withanti-inflammatory properties, but he was still getting occasional goutsymptoms. During one episode of gout pain and inflammation, thefollowing treatment was provided:

-   -   4 capsules of celery seed extract—two taken twice per day,    -   5 capsules of cherry fruit extract—two taken in the morning, one        at lunch, and two in the evening, and    -   3 tablets of lithium orotate—one taken three times a day.        During the first four days of treatment the man in addition took        ½ tablet of 0.6 mg colchicine twice a day and massaged the big        toe joint with Three Angels Liniment from Blue Poppy Herbs three        to four times per day. All the gout symptoms were gone by three        days after the initiation of treatment. After four additional        days of treatment the treatment was changed to the same        treatment as described in Example 1. The man has not experienced        any further gout symptoms, or any adverse effects from the        treatment, for more than four weeks.

In the past, this man had used medication consisting of a full dose of50 mg indomethacin three times a day and one tablet twice a day of 0.6mg colchicine to relieve the symptoms of similar gout pain andinflammation. The gout symptoms would resolve within 3-5 days on thismedication regime, but would re-occur within a few months after themedication was discontinued.

Example 3

16 capsules of celery seed extract, 20 capsules of cherry fruit extract,and 12 tablets of lithium orotate are emptied and mixed together in amortar and pestle. All of the resulting homogeneously mixed powder isplaced evenly into 12 empty size 000 gelatin capsules, with noadditional filler. Each gelatin capsule thus contains 100 mg celery seedextract, approx. 833 mg cherry fruit extract, and 4.9 mg lithium aslithium orotate.

A patient with gout takes the capsules, 1 capsule with each of 3 mealsper day, for two to four days, until all gout symptoms are abated. NoNSAIDS nor colchicine are taken during this time, so there is nogastrointestinal distress as a result of the treatment.

Example 4

60 capsules of celery seed extract, 60 capsules of cherry fruit extract,and 40 tablets of lithium orotate are emptied into a food processor. Themixture is processed into a homogeneous fine powder, then filled into 60clear size 00 vegetarian capsules using a Capsuline®-60 Capsule FillerMachine. A human patient who has had gout in the past, but is currentlysymptom-free, takes 3 of these filled capsules daily, 1 with each meal.No gout symptoms develop during the period of treatment. No adverseeffects of the treatment are felt by the patient. Additionally thepatient notices improved mental functioning, including improved sleep,better concentration and memory, and more stable moods after about threemonths of continued treatment.

1. A method for relieving or preventing symptoms associated with uricacid crystals, comprising consuming a formulation that supports three ormore processes that reduce a symptom due to uric acid crystals in abody, the processes comprising: 1) a process that inhibits formation ofuric acid in the body; 2) a process that increases elimination of uricacid from the body; and 3) a process that interferes with formation ofuric acid crystals in the body.
 2. The method of claim 1, wherein theformulation comprises an extract of celery, an extract of cherry, and alithium salt.
 3. The method of claim 2, wherein the extract of celery isfrom a seed.
 4. The method of claim 2, wherein the extract of cherry isfrom a fruit.
 5. The method of claim 2, wherein the lithium salt isselected from lithium orotate, lithium aspartate, lithium proteinate,lithium citrate, lithium carbonate, and mixtures thereof.
 6. The methodof claim 2, wherein the formulation comprises from 25 to 200 mg ofextract of celery, from 100 to 1500 mg extract of cherry, and from 1.5to 10 mg of lithium in the lithium salt; and wherein the formulation isconsumed from one to four times per day.
 7. The method of claim 1,wherein the extract of celery is standardized to contain at least 50%3-n-butylphthalide calculated as total phthalides.
 8. The method ofclaim 4, wherein the cherry fruit extract is sweet cherry (Prunus avium)fruit extract of at least 5:1.
 9. A formulation for relieving orpreventing symptoms associated with uric acid crystals, comprising: a.an extract of celery; b. an extract of cherry; and c. a lithium salt.10. The formulation of claim 9, wherein the extract of celery is from aseed.
 11. The formulation of claim 9, wherein the extract of celery isstandardized to contain at least 50% 3-n-butylphthalide calculated astotal phthalides.
 12. The formulation of claim 9, wherein the extract ofcherry is from a fruit.
 13. The formulation of claim 9, wherein theextract of cherry is sweet cherry (Prunus avium) fruit extract of atleast a 5:1 concentrate.
 14. The formulation of claim 9, comprising from25 to 200 mg of extract of celery, from 100 to 1500 mg extract ofcherry, and from 1.5 to 10 mg of lithium in the lithium salt in amedicament selected from the group consisting of a tablet, a capsule, apill, a softgel, a suspension, and a powder.
 15. The formulation ofclaim 9, comprising less than 5 wt % inert filler.
 16. The formulationof claim 9, that is a high dose formulation for acute gout phasetreatment.
 17. The formulation of claim 9, that is a low doseformulation for preventative treatment of gout, kidney stones, or acombination thereof.
 18. The formulation of claim 9, wherein theformulation is a mixture made of dry particles.
 19. A process to make aformulation for relieving or preventing symptoms associated with uricacid crystals, comprising: a. mixing together: i. a material that whenconsumed inhibits formation of uric acid in a body; ii. a material thatwhen consumed increases elimination of uric acid from the body; iii. amaterial that when consumed interferes with formation of uric acidcrystals in the body; and b. forming the mixture of step (a) into amedicament.
 20. The process of claim 19, wherein the material that whenconsumed inhibits formation of uric acid in the body is celery seedextract; the material that when consumed increases elimination of uricacid from the body is cherry fruit extract; and wherein the materialthat when consumed interferes with formation of uric acid crystals inthe body is lithium salt.